Field of the Invention
This invention relates to methods of treatment of coronary and peripheral artery disease of human patients with bioresorbable polymer scaffolds, in particular, treatments in which shear stress of blood flow past such scaffolds effects neointimal formation.
Description of the State of the Art
This invention relates generally to methods of treatment with radially expandable endoprostheses that are adapted to be implanted in a bodily lumen. An “endoprosthesis” corresponds to an artificial device that is placed inside the body. A “lumen” refers to a cavity of a tubular organ such as a blood vessel. A stent is an example of such an endoprosthesis. Stents are generally cylindrically shaped devices that function to hold open and sometimes expand a section or segment of a blood vessel or other anatomical lumen such as urinary tracts and bile ducts. Stents are often used in the treatment of atherosclerotic stenosis in blood vessels. “Stenosis” refers to a narrowing or constriction of a bodily passage or orifice. In such treatments, stents reinforce body vessels and prevent restenosis following angioplasty in the vascular system. “Restenosis” refers to the reoccurrence of stenosis in a blood vessel or heart valve after it has been treated (as by balloon angioplasty, stenting, or valvuloplasty) with apparent success.
Stents are typically composed of a scaffold or scaffolding that includes a pattern or network of interconnecting structural elements or struts, formed from wires, tubes, or sheets of material rolled into a cylindrical shape. This scaffold gets its name because it physically holds open and, if desired, expands the wall of a passageway in a patient. Typically, stents are capable of being compressed or crimped onto a catheter from a fabricated diameter to a reduced diameter so that they can be delivered to and deployed at a treatment site.
Delivery includes inserting the stent through small lumens using a catheter and transporting it to the treatment site. Deployment includes expanding the stent to a larger target diameter once it is at the desired location. During deployment the stent makes contact with the vessel wall as it expands and expands the vessel to the larger target diameter. Mechanical intervention with stents has reduced the rate of restenosis as compared to balloon angioplasty.
Stents are used not only for mechanical intervention but also as vehicles for providing biological therapy. Biological therapy uses medicated stents to locally administer a therapeutic substance to a blood vessel. The therapeutic substance can also mitigate an adverse biological response to the presence of the stent. For example, the stent can deliver an antiproliferative agent to the vessel to prevent or mitigate neointimal proliferation caused by the stent implantation which could result in narrowing of the vessel at the site of the stent implantation. Additionally or alternatively, an anti-inflammatory agent can be delivered to reduce inflammation to the vessel wall due to the stent implantation.
A medicated stent may be fabricated by coating the surface of either a metallic or polymeric scaffolding with a polymeric carrier that includes an active or bioactive agent or drug. Polymeric scaffolding may also serve as a carrier of an active agent or drug.
The stent must be able to satisfy a number of mechanical requirements. The stent must have sufficient radial strength so that it is capable of withstanding the structural loads, namely radial compressive forces imposed on the stent as it supports the walls of a vessel at the expanded target diameter. Radial strength, which is the ability of a stent to resist radial compressive forces, relates to a stent's radial yield strength and radial stiffness around a circumferential direction of the stent. A stent's “radial yield strength” or “radial strength” (for purposes of this application) may be understood as the compressive loading, which if exceeded, creates a yield stress condition resulting in the stent diameter not returning to its unloaded diameter, i.e., there is irrecoverable deformation of the stent. When the radial yield strength is exceeded the stent is expected to yield more severely and only a minimal force is required to cause major deformation.
Once expanded, the stent must adequately provide lumen support during a time required for treatment in spite of the various forces that may come to bear on it, including the cyclic loading induced by the beating heart. In addition, the stent must possess sufficient flexibility with a certain resistance to fracture.
Stents made from biostable or non-erodible materials, such as metals, have become the standard of care for percutaneous coronary intervention (PCI) as well as in peripheral applications, such as the superficial femoral artery (SFA). Such stents have been shown to be capable of preventing early and later recoil and restenosis. These permanent stents include bare metal stents and drug eluting stents which include a metallic base or scaffold with a polymer and drug coating.
In order not to affect healing of a diseased blood vessel, the presence of the stent is necessary only for a limited period of time. There are certain disadvantages to the presence of a permanent implant in a vessel such as compliance mismatch between the stent and vessel and risk of embolic events such as late stint thrombosis. To alleviate such disadvantages, a stent can be made from materials that erode or disintegrate through exposure to conditions within the body. Thus, erodible portions of the stent can disappear from the implant region after the treatment is completed, leaving a healed vessel. Stents fabricated from biodegradable, bioabsorbable, bioresorbable, and/or bioerodable materials such as bioabsorbable polymers can be designed to completely erode only after the clinical need for them has ended.
Polymers tend to have a lower strength on a per unit weight or volume basis than metals. As a result, the thickness of structural members or struts of a polymer scaffold tends to larger that metal stents. For example, a polymer scaffold for coronary applications may have a thickness, width, or both greater than 100 microns, greater than 120 microns, 100-200 microns, 120-180, 130-170, or 140-160 microns. Metallic stent struts may have a thickness, width, or both less than 100 microns, less than 80 microns, or 60 to 80 microns.
When a scaffold or stent is implanted, the struts of the stent project into the blood vessel. Since the struts project into the flow path of blood, the struts can create a resistance to and disrupt blood flow. Cumulative evidence, derived from intravascular ultrasound-based studies, has demonstrated a strong association between local endothelial shear stress (ESS) patterns and neointimal formation in bare metal stents, whereas in drug eluting stents there is contradictory data about the effect of ESS on vessel wall healing process. The effect of ESS on neointimal development following a bioresorbable scaffold implantation has remained unclear.